1-230713085-C-T

Variant names:

• chr1-230713085-C-T
• rs3889728
• NM_001384479.1:c.-31+1001G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):​c.-31+1001G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,088 control chromosomes in the GnomAD database, including 5,028 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (5028 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 17 publications found

Genes affected

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

AGT Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

CAPN9-AS1 (HGNC:58238):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.-31+1001G>A		intron	N/A	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.-30-2232G>A		intron	N/A	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.-31+1001G>A		intron	N/A	ENSP00000355627.5	P01019
	AGT	ENST00000680041.1		c.-156+1001G>A		intron	N/A	ENSP00000504866.1	P01019
	AGT	ENST00000681269.1		c.-30-2232G>A		intron	N/A	ENSP00000505985.1	P01019

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37116 AN: 151966 Hom.: 5032 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.244 AC: 37116 AN: 152088 Hom.: 5028 Cov.: 32 AF XY: 0.248 AC XY: 18438 AN XY: 74346

African (AFR) AF: 0.159 AC: 6609 AN: 41494

American (AMR) AF: 0.326 AC: 4994 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2683 AN: 5150

South Asian (SAS) AF: 0.282 AC: 1358 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2716 AN: 10568

Middle Eastern (MID) AF: 0.144 AC: 42 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17185 AN: 67982

Other (OTH) AF: 0.243 AC: 513 AN: 2110

Alfa AF: 0.252 Hom.: 13181

Bravo AF: 0.248

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.68
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3889728; hg19: chr1-230848831;